Gastric Bypass Surgery Enhances Glucagon-Like Peptide 1–Stimulated Postprandial Insulin Secretion in Humans

Salehi, Marzieh; Prigeon, Ronald L.; D’Alessio, David A.

doi:10.2337/db11-0203

Cited by 296 publications

(301 citation statements)

References 31 publications

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“…Others (32) have reported that surgical restoration of gastric restriction to slow down the release of glucose into the intestine improved hypoglycaemia. However, in a recent study, the exaggerated effect of GLP1 on postprandial insulin secretion in surgical subjects was not significantly different from those with and without recurrent hypoglycaemia (14).…”

Section: Incretin Hormones and The Pancreatic Insular Axismentioning

confidence: 76%

“…The improvement in diabetes following GBS is thought to result from decreased insulin resistance associated with caloric restriction and weight loss and enhanced insulin secretion through an altered enteroinsular axis (12,13,14), and even possibly through the activation of dormant b-cells (15). Reports of PHH following GBS first appeared in 2004 (3,16).…”

Section: Discussionmentioning

confidence: 99%

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Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass: the pathophysiological role of GLP1 and its response to a somatostatin analogue

Myint

Greenfield²,

Farooqi³

et al. 2012

European Journal of Endocrinology

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Background: Spontaneous hyperinsulinaemic hypoglycaemia following gastric bypass surgery (GBS) is increasingly recognised. However, its pathophysiology remains unclear. Some patients require pancreatectomy. Medical therapy with calcium channel blockers, acarbose and diazoxide has been reported to be beneficial but has variable adherence and response. Method: We demonstrate the role of GLP1, counter-regulatory hormones and the subsequent response of GLP1 to somatostatin analogue therapy in a 42-year-old woman with persistent neuroglycopaenia 6 years after GBS. Plasma GLP1, insulin and glucose were measured for 5 h on three settings: i) a 75 g oral glucose tolerance test (OGTT); ii) a standard liquid test meal (LTM); and iii) an OGTT 30 min after a s.c. injection of 100 mg octreotide. Results: In comparison with obese non-diabetic controls, the patient had an elevated fasting and a markedly enhanced GLP1 response during the OGTT, followed by an exaggerated insulin response and a subsequent low glucose level. The GLP1 response to a LTM was similar but greater. Octreotide given prior to the OGTT attenuated both the GLP1 and insulin responses and abolished hypoglycaemia. Octreotide therapy significantly improved the patient's neuroglycopaenic symptoms. The hormone profile was reassessed after 6 months following the LTM preceded by octreotide injection. Peak GLP1 and insulin responses were less pronounced than pretreatment responses and without hypoglycaemia. The patient was treated with lanreotide and had remained symptom-free and euglycaemic for 4 years. Conclusion: An exaggerated incretin response following altered gastrointestinal anatomy was the likely cause of hypoglycaemia in our GBS patient. Somatostatin successfully suppressed this response acutely and in the long term, thereby avoiding pancreatectomy and its sequelae.

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Section: Incretin Hormones and The Pancreatic Insular Axismentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass: the pathophysiological role of GLP1 and its response to a somatostatin analogue

Myint

Greenfield²,

Farooqi³

et al. 2012

European Journal of Endocrinology

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“…This time lag was much more pronounced after RYGB. The later decrease in plasma glucose was partly due to decreasing oral glucose R a , but more importantly also to enhanced and prolonged glucose disappearance in response to hypersecretion of insulin, possibly due to exaggerated GLP-1 release [8,9]. As a consequence, the glucose concentration had already reached the basal level 2 h postprandially, followed by a brief period of hypoglycaemia.…”

Section: Discussionmentioning

confidence: 98%

Effects of gastric bypass surgery on glucose absorption and metabolism during a mixed meal in glucose-tolerant individuals

et al. 2013

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Aims/hypothesis Roux-en-Y gastric bypass surgery (RYGB) improves glucose tolerance in patients with type 2 diabetes, but also changes the glucose profile in response to a meal in glucose-tolerant individuals. We hypothesised that the driving force for the changed postprandial glucose profiles after RYGB is rapid entry of glucose into the systemic circulation due to modified gastrointestinal anatomy, causing hypersecretion of insulin and other hormones influencing glucose disappearance and endogenous glucose production. Methods We determined glucose absorption and metabolism and the rate of lipolysis before and 3 months after RYGB in obese glucose-tolerant individuals using the double-tracer technique during a mixed meal. Results After RYGB, the postprandial plasma glucose profile changed, with a higher peak glucose concentration followed by a faster return to lower than basal levels. These changes were brought about by changes in glucose kinetics: (1) a more rapid appearance of ingested glucose in the systemic circulation, and a concomitant increase in insulin and glucagon-like peptide-1 secretion; (2) postprandial glucose disappearance was maintained at a high rate for a longer time after RYGB. Endogenous glucose production was similar before and after surgery. Postoperative glucagon secretion increased and showed a biphasic response after RYGB. Adipose tissue basal rate of lipolysis was higher after RYGB. Conclusions/interpretation A rapid rate of absorption of ingested glucose into the systemic circulation, followed by increased insulin secretion and glucose disappearance appears to drive the changes in the glucose profile observed after RYGB, while endogenous glucose production remains unchanged. Trial registration ClinicalTrials.gov NCT01559792.

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“…Using exendin(9-39), it has been shown that endogenous GLP-1 inhibits glucagon, stimulates insulin, and contributes to the incretin effect in both healthy subjects and patients with T2D (13)(14)(15). So far, studies employing the GLP-1R antagonist after RYGB revealed that GLP-1 contributed to an exaggerated insulin response after RYGB (16)(17)(18). b-Cell glucose sensitivity was doubled within 3 months after surgery, reversed by exendin(9-39) (17).…”

mentioning

confidence: 99%

GLP-1—A Candidate Humoral Mediator for Glucose Control After Roux-en-Y Gastric Bypass

Schirra

Göke

2014

Diabetes

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The worldwide increase in obesity is associated with a higher prevalence of type 2 diabetes (T2D), and severe obesity occurs with the greatest risk (1). Bariatric surgery is currently the most effective treatment not only for weight loss but also for prevention or treatment of T2D in such patients (2). It leads to remission or improvement of T2D in the majority of morbidly obese (3,4). Roux-en-Y gastric bypass (RYGB) is one of the most frequently performed procedures. With RYGB, the stomach is reduced to a small proximal pouch (30-50 mL) and anastomosed to the jejunum, thereby bypassing the majority of the stomach and duodenum. After RYGB, T2D improves rapidly often before significant weight loss occurs. The mechanisms behind this phenomenon are not clearly resolved. Caloric restriction contributes. Extreme caloric restriction to the limit just tolerated in patients after surgery improved insulin resistance in obese subjects similarly as found in after the first week after RYGB (5). Of interest, the malabsorptive component of the RYGB procedure approximately accounts only for up to 11% of the total reduction in combustible energy absorption (6). Changes of adipokine-induced inflammation and insulin resistance (7) and reduction of branched-chain amino acids correlating with insulin resistance (8) have been proposed as further mechanisms operating after bariatric surgery complementing the sole weight loss.A popular hypothesis points to an antidiabetic effect after RYGB of postprandially exaggeratedly released gut peptides, such as glucagon-like peptide 1 (GLP-1), already starting early after surgery. The release of GLP-1 depends on gastric emptying (GE) velocity (9). It lowers postprandial glycemia by stimulation of insulin, inhibition of glucagon secretion, and delay of GE. For example, Laferrère et al. (10) reported a sixfold increase in GLP-1 plasma levels and a fivefold increase of the incretin effect in obese patients with T2D 1 month after RYGB. In this issue, Shah et al. (11) addressed the contribution of endogenous GLP-1 to the meal-induced glucose metabolism, islet secretion, and GE after RYGB in 12 nondiabetic obese patients 5 6 0.9 years after RYGB and 8 weightmatched control subjects twice using the GLP-1 receptor (GLP-1R) antagonist exendin(9-39). After ingestion of a 220 kcal mixed-meal, glucose metabolism was measured using the isotope dilution method. Indices of insulin action and b-cell glucose responsitivity and the resulting glucose disposition indices were calculated using the oral minimal model. GE was measured by scintigraphy. As expected, GE (gastric pouch in the post-RYGB subjects) was greatly accelerated, leading to a several-fold increase in postprandial GLP-1, insulin, and C-peptide responses after RYGB. The GLP-1R antagonist increased the postprandial glucose excursions in both groups. Exendin(9-39) decreased insulin and C-peptide concentrations in subjects post-RYGB by about 30% with no effect in control subjects. The calculated b-cell response to glucose was significantly reduced in b...

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Gastric Bypass Surgery Enhances Glucagon-Like Peptide 1–Stimulated Postprandial Insulin Secretion in Humans

Cited by 296 publications

References 31 publications

Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass: the pathophysiological role of GLP1 and its response to a somatostatin analogue

Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass: the pathophysiological role of GLP1 and its response to a somatostatin analogue

Effects of gastric bypass surgery on glucose absorption and metabolism during a mixed meal in glucose-tolerant individuals

GLP-1—A Candidate Humoral Mediator for Glucose Control After Roux-en-Y Gastric Bypass

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